Metachromatic Leukodystrophy

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Metachromatic leukodystrophyis an inherited disorder characterized by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system).

Causes: Metachromatic leukodystrophy (MLD) is usually caused by the lack of an important enzyme called arylsulfatase A. Because this enzyme is missing, chemicals called sulfatides build up in and damage the nervous system, kidneys, gallbladder, and other organs. In particular, the chemicals damage the protective sheaths that surround nerve cells. The disease is passed down through families (inherited). You must get a copy of the defective gene from both your parents to have the disease. Parents can each have the defective gene, but not have MLD. A person with one defective gene is called a "carrier." Children who inherit only one defective gene from one parent will be a carrier, but usually will not develop MLD. When two carriers have a child, there is a 25% chance that the child will get both genes and have MLD. Late infantile MLD symptoms usually begin by ages 1 - 2. Symptoms: Juvenile MLD symptoms usually begin between ages 4 and 12, Abnormal high muscle tone, abnormal muscle movements, Behaviour problems, Decreased mental function, Decreased muscle tone, Difficulty walking, Feeding difficulties, Frequent falls, Inability to perform normal tasks, Incontinence, Irritability, Loss of muscle control, Nerve function problems, Personality changes, Poor school performance, Seizures, Speech difficulties, slurring, Swallowing difficulty.

Diagnosis: Tests that may be done include: Blood or skin culture to look for low arylsulfatase A activity, Blood test to look for low arylsulfatase A enzyme levels, CT scan, DNA testing for the ARSA gene, MRI, Nerve biopsy, Nerve signalling studies, Urinalysis, Urine chemistry. Treatment: There is no cure for MLD. Care focuses on treating the symptoms and preserving the patient's quality of life with physical and occupational therapy. Prevention: Genetic counselling is recommended if you have a family history of this disorder.

Mesenchymal stem cells (MSCs) have recently made significant progress with multiple clinical trials targeting modulation of immune responses, regeneration of bone, cartilage, myocardia, and diseases like Metachromatic leukodystrophy and Hurler syndrome. On the other hand, the use of human embryonic and induced pluripotent stem cells (hPSCs) in clinical trials is rather limited mainly due to safety issues. Only two clinical trials, retinal pigment epithelial transplantation and treatment of spinal cord injury were reported. Cell doses per treatment can range between 50,000 and 6 billion cells. The current 2-dimensional tissue culture platform can be used when low cell doses are needed and it becomes impractical when doses above 50 million are needed. This demand for future cell therapy has reinvigorated interests in the use of the microcarrier platform for generating stem cells in a scalable 3-dimensional manner. Microcarriers developed for culturing adherent cell lines in suspension have been used mainly in vaccine production and research purposes.